1. Field of the Invention
The present invention relates to a method and apparatus for contemporaneous application of laser energy and localized delivery of pharmacologic therapy to a site within a body lumen. More specific applications of the present invention relate to a method and apparatus for localized treating of vascular thrombosis disorders, atherosclerosis, and tumors.
2. Description of Prior Art
Atherosclerosis, which is a major cause of cardiovascular disease, resulting in heart attacks, is characterized by the progressive accumulation of atherosclerotic deposits (known as plaque) on the inner walls of the arteries. As a result, blood flow is restricted and there is an increased likelihood of clot formation that can partially or completely block or occlude an artery, causing a heart attack. Arteries narrowed by atherosclerosis that cannot be treated effectively by drug therapy are typically treated by medical procedures designed to increase blood flow, including highly invasive procedures such as coronary artery bypass surgery and less invasive procedures such as balloon angioplasty, atherectomy and laser angioplasty.
Bypass surgery involves opening the patient's chest and transferring a vein cut from the patient's leg to the heart to construct a detour around the occluded artery. Bypass surgery requires prolonged hospitalization and an extensive recuperation period. Furthermore, bypass surgery also exposes the patient to a risk of major surgical complications. Balloon angioplasty is a less invasive and less costly alternative to bypass surgery and is performed in a hospital cardiac catheterization laboratory by an interventional cardiologist. In this procedure, a balloon-tipped catheter is inserted into a blood vessel through a small incision in the patient's arm or leg. The physician uses a guide catheter to feed the balloon through the patient's blood vessels to the occluded artery. At that point, a guidewire is inserted across the deposits of atherosclerotic plaque, known as lesions, to provide a pathway for the balloon catheter. The deflated balloon is advanced over the guidewire, positioned within the occluded area and inflated and deflated several times. This inflation and deflation usually tears the plaque and expands the artery beyond its point of elastic recoil. Thus, although no plaque is removed, the opening through which blood flows is enlarged.
Atherectomy employs a rotating mechanical device mounted on a catheter to cut and remove plaque from a diseased artery. Although atherectomy, unlike balloon angioplasty, removes plaque from coronary arteries, existing atherectomy devices are not effective in treating certain types of lesions.
Laser angioplasty removes plaques by using light, in varying wavelengths ranging from ultraviolet to infrared, that is delivered to the lesion by a fiber optic catheter. Early attempts to develop a laser angioplasty system used continuous wave thermal lasers that generated heat to vaporize plaque. These laser systems caused charring and significant thermal damage to healthy tissue surrounding the lesion. As a result, thermal laser systems have generally been regarded as inappropriate for use in the coronary arteries. In contrast, excimer lasers use ultraviolet light to break the molecular bonds of atherosclerotic plaque, a process known as photoablation. Excimer lasers use electric, ally excited xenon and chloride gases to generate an ultraviolet laser pulse with a wavelength of 308 nanometers. This wavelength of ultraviolet light is absorbed by the proteins and lipids that comprise plaque, resulting in precise ablation of plaque and the restoration of blood flow without significant thermal damage to surrounding tissue. The ablated plaque is converted into carbon dioxide and other gases and minute particulate matter that can be easily eliminated.
In laser angioplasty, conventional light guides using fiber optics are used to direct laser energy onto arterial plaque formations to ablate the plaque or thrombus and remove the occlusion. Individual optically conducting fibers are typically made of fused silica or quartz, and are generally fairly inflexible unless they are very thin. A thin fiber flexible enough to pass through a lumen halving curves of small radius, such as through arterial lumens from the femoral or the brachial artery to a coronary artery, typically projects a beam of laser energy of very small effective diameter, capable of producing only a very small opening in the occlusion. Moreover, the energy is attenuated over relatively small distances as it passes within a thin fiber. Small diameter fibers can mechanically perforate vessels when directed against the vessel wall as they are passed within the vessel toward the site.
In order to bring a sufficient quantity of energy from the laser to the thrombus or plaque, light guides proposed for use in laser angioplasty usually include a number of very thin fibers, each typically about 50 to 200 microns in diameter, bundled together or bound in a tubular matrix about a central lumen, forming a catheter. Laser energy emerging from a small number of fibers bundled together produces lumens of suboptimal diameter which can require subsequent enlargement by, for example, balloon dilation. Such devices do not always remove an adequate quantity of matter from the lesion, and their uses are generally limited to providing access for subsequent conventional balloon angioplasty.
Although individual fibers of such small dimensions are flexible enough to negotiate curves of fairly small radius, a bundle of even a few such fibers is less flexible and more costly. Coupling mechanisms for directing laser energy from the source into the individual fibers in a light guide made up of multiple small fibers can be complex. Improper launch of the laser energy into such a light guide can destroy the fibers. The directing of laser energy into arteries or veins thus far has been limited to two-dimensional imaging with fluoroscopy. Frequently, it is not possible to distinguish whether the laser catheter is contacting plaque, normal tissue, or thrombus--all of which have very different therapeutic consequences as well as possible adverse side effects.
An alternative to conventional optical fiber technology using fused silica fibers or fiber bundles, is the use of fluid core light guides to transmit light into the body, as discussed by Gregory et al. in the article "Liquid Core Light Guide for Laser Angioplasty", IEEE Journal of Quantum Electronics, Vol. 26, No. 12, December 1990, incorporated herein. While fluid-core light guides may offer improvements of fused silica fibers or bundles, initial animal and clinical studies indicate inadequate or only partial removal of thrombus or athlerosclerotic material, and a recurrence of athlerosclerosis after treatment.
Another approach to treating atherosclerosis orthrombosis is to degrade thrombi and plaque by treatment with various pharmacologic agents. Many techniques currently exist for delivering medicant and other active agents to body tissue. These include: oral administration, direct injection into body tissue, and intravenous administration which involves introducing the active agent directly into the blood stream. These delivery mechanisms are systemic, in that they deliver the active agent via the bloodstream throughout the entire body. Effective pharmacologic or drug therapy requires achieving adequate concentrations of an active drug at the site of desired treatment without producing concentrations of the drug elsewhere in the body that create unwanted or dangerous side effects.
Workers in the field have discovered that many effective drugs which are capable of treating or curing disease cannot be effectively delivered systemically because the concentrations necessary for effective treatment produce adverse side effects in other parts of the body. For example, in the case of arterial and venous thrombosis, workers in the field have identified many potent agents which are capable of degrading thrombi, but clinical application of these agents has been limited by bleeding complications which can result in substantially increased morbidity and mortality. Moreover, even clinically approved agents such as streptokinase, urokinase, recombinant tissue plasminogen activators or even heparin have limited efficacy in treating acute myocardial infarction and other thrombotic disorders because they can produce systemic bleeding complications.
One approach to reducing systemic side effects is to introduce a catheter percutaneously, through the skin, near the thrombotic site under fluoroscopic guidance. The active agent is then infused in high concentrations and flowed by the thrombus. There are, however, practical limits to the duration of such treatment. Prolonged infusion will eventually produce a total accumulated systemic dose of the agent sufficient to create adverse side effects. Enzymatic degradation is in large part dependent upon the surface area of the thrombus which is exposed to the enzyme--which is limited to current infusion of enzymes which flow by the thrombus. In addition to the great cost of such an infusion, the prolonged indwelling of the catheter increases morbidity. The ability to administer an active agent locally to the thrombotic site without systemically affecting other tissues or creating complications, would greatly enhance the ability to effectively treat arterial and venous thrombus.
Another application for delivering an active agent to an internal body tissue is in treating cancerous tumors. The objective of such treatment is to concentrate as much of the cancer drug or gene product in the tumor as possible. Typically, workers in the field administer cancer drugs systemically through the blood stream and then use various means to localize the drug in the cancerous tumor. Nevertheless, amounts of the drug still circulate through the blood stream in sufficient concentrations to produce adverse side effects and therefore limit the dosages of the drug which can be safely administered.
Accordingly, a need remains for a method and apparatus for locally delivering an active agent in conjunction with delivering laser energy to internal body tissue. There is a further need for such an apparatus and method for treating atherosclerosis, thrombosis, cancerous tumors, and other internal body tissue.